Extensional viscosity to promote safe swallowing of food boluses

ABSTRACT

Nutritional products having improved cohesiveness of food boluses and methods of making and using same are provided. The nutritional products may include nutritional compositions and high molecular weight, water-soluble polymers such that the nutritional products have extensional viscosities that provide improved cohesiveness to the nutritional products and Trouton ratios of at least 6. Methods of administering such nutritional products to patients having impaired swallowing ability and/or dysphagia are also provided.

PRIORITY CLAIMS

The present application is a Continuation of U.S. patent applicationSer. No. 14/002,052 filed Sep. 16, 2013, which is a National Stage ofInternational Application No. PCT/EP2012/053533 filed Mar. 1, 2012,which claims priority to U.S. Provisional Application No. 61/570,879filed Dec. 15, 2011, U.S. Provisional Application No. 61/469,852 filedMar. 31, 2011, U.S. Provisional Application No. 61/447,745 filed Mar. 1,2011, and European Application No. 11193803.1 filed Dec. 15, 2011, theentire contents of which are incorporated herein by reference.

BACKGROUND

The present disclosure is directed to nutritional products and methodsfor administering same. More specifically, the present disclosure isdirected to nutritional products for promoting safer swallowing of foodboluses for patients having swallowing conditions or being impairedthereby.

Dysphagia is the medical term for the symptom of difficulty inswallowing. Epidemiological studies estimate a prevalence rate of 16% to22% among individuals over 50 years of age.

Esophageal dysphagia affects a large number of individuals of all ages,but is generally treatable with medications and is considered a lessserious form of dysphagia. Esophageal dysphagia is often a consequenceof mucosal, mediastinal, or neuromuscular diseases. Mucosal (intrinsic)diseases narrow the lumen through inflammation, fibrosis, or neoplasiaassociated with various conditions (e.g., peptic stricture secondary togastroesophageal reflux disease, esophageal rings and webs [e.g.,sideropenic dysphagia or Plummer-Vinson syndrome], esophageal tumors,chemical injury [e.g., caustic ingestion, pill esophagitis,sclerotherapy for varices], radiation injury, infectious esophagitis,and eosinophilic esophagitis). Mediastinal (extrinsic) diseases obstructthe esophagus by direct invasion or through lymph node enlargementassociated with various conditions (tumors [e.g., lung cancer,lymphoma], infections [e.g., tuberculosis, hi stoplasmosis], andcardiovascular [dilated auricula and vascular compression]).Neuromuscular diseases may affect the esophageal smooth muscle and itsinnervation, disrupting peristalsis or lower esophageal sphincterrelaxation, or both, commonly associated with various conditions(achalasia [both idiopathic and associated with Chagas disease],scleroderma, other motility disorders, and a consequence of surgery[i.e., after fundoplication and antireflux interventions]). It is alsocommon for individuals with intraluminal foreign bodies to experienceacute esophageal dysphagia.

Oral pharyngeal dysphagia, on the other hand, is a very seriouscondition and is generally not treatable with medication. Oralpharyngeal dysphagia also affects individuals of all ages, but is moreprevalent in older individuals. Worldwide, oral pharyngeal dysphagiaaffects approximately 22 million people over the age of 50. Oralpharyngeal dysphagia is often a consequence of an acute event, such as astroke, brain injury, or surgery for oral or throat cancer. In addition,radiotherapy and chemotherapy may weaken the muscles and degrade thenerves associated with the physiology and nervous innervation of theswallow reflex. It is also common for individuals with progressiveneuromuscular diseases, such as Parkinson's disease, to experienceincreasing difficulty in swallowing initiation. Representative causes oforopharyngeal dysphagia include those associated neurological illnesses(brainstem tumors, head trauma, stroke, cerebral palsy, Guillain-Barresyndrome, Huntington's disease, multiple sclerosis, polio, post-poliosyndrome, Tardive dyskinesia, metabolic encephalopathies, amyotrophiclateral sclerosis, Parkinson's disease, dementia), infectious illnesses(diphtheria, botulism, Lyme disease, syphilis, mucositis [herpetic,cytomegalovirus, candida, etc.]), autoimmune illnesses (lupus,scleroderma, Sjogren's syndrome), metabolic illnesses (amyloidosis,cushing's syndrome, thyrotoxicosis, Wilson's disease), myopathicillnesses (connective tissue disease, dermatomyositis, myastheniagravis, myotonic dystrophy, oculopharyngeal dystrophy, polymyositis,sarcoidosis, paraneoplastic syndromes, inflammatory myopathy),iatrogenic illnesses (medication side effects [e.g., chemotherapy,neuroleptics, etc.], post surgical muscular or neurogenic, radiationtherapy, corrosive [pill injury, intentional]), and structural illnesses(cricopharyngeal bar, Zenker's diverticulum, cervical webs,oropharyngeal tumors, osteophytes and skeletal abnormalities, congenital[cleft palate, diverticulae, pouches, etc.]).

Dysphagia is not generally diagnosed although the disease has majorconsequences on patient health and healthcare costs. Individuals withmore severe dysphagia generally experience a sensation of impairedpassage of food from the mouth to the stomach, occurring immediatelyafter swallowing. Among community dwelling individuals, perceivedsymptoms may bring patients to see a doctor. Among institutionalizedindividuals, health care practitioners may observe symptoms or hearcomments from the patient or his/her family member suggestive ofswallowing impairment and recommend the patient be evaluated by aspecialist. As the general awareness of swallowing impairments is lowamong front-line practitioners, dysphagia often goes undiagnosed anduntreated. Yet, through referral to a swallowing specialist (e.g.,speech language pathologist), a patient can be clinically evaluated anddysphagia diagnosis can be determined.

The general awareness of swallowing impairments is low among front-linepractitioners. Many people (especially those who are elderly) sufferwith undiagnosed and untreated swallowing impairments. One reason isthat front-line community care practitioners (e.g., generalpractitioners/geriatricians, home care nurses, physical therapists,etc.) do not typically screen for the condition. If they are aware ofthe severity of swallowing impairments, they commonly do not use anevidence-based method of screening. Furthermore, office-based assessmentof dysphagia rarely occurs.

Severity of dysphagia may vary from: (i) minimal (perceived) difficultyin safely swallowing foods and liquids, (ii) an inability to swallowwithout significant risk for aspiration or choking, and (iii) a completeinability to swallow. Commonly, the inability to properly swallow foodsand liquids may be due to food boluses being broken up into smallerfragments, which may enter the airway or leave unwanted residues in theoropharyngeal and/or esophageal tract during the swallowing process(e.g., aspiration). If enough material enters the lungs, it is possiblethat the patient may drown on the food/liquid that has built up in thelungs. Even small volumes of aspirated food may lead to bronchopneumoniainfection, and chronic aspiration may lead to bronchiectasis and maycause some cases of asthma.

“Silent aspiration,” a common condition among elderly, refers to theaspiration of the oropharyngeal contents during sleep. People maycompensate for less-severe swallowing impairments by self-limiting thediet. The aging process itself, coupled with chronic diseases such ashypertension or osteoarthritis, predisposes elderly to (subclinical)dysphagia that may go undiagnosed and untreated until a clinicalcomplication such as pneumonia, dehydration, malnutrition (and relatedcomplications) occurs. Yet, the differential diagnosis of ‘aspirationpneumonia’ is not necessarily indicated as a result of current carepractices.

The economic costs of dysphagia are associated with hospitalization,re-hospitalization, loss of reimbursement due to pay for performance(“P4P”), infections, rehabilitation, loss of work time, clinic visits,use of pharmaceuticals, labor, care taker time, childcare costs, qualityof life, increased need for skilled care. Dysphagia and aspirationimpact quality of life, morbidity and mortality. Twelve-month mortalityis high (45%) among individuals in institutional care who have dysphagiaand aspiration. The economic burden of the clinical consequences arisingfrom lack of diagnosis and early management of dysphagia aresignificant.

Pneumonia is a common clinical consequence of dysphagia. The conditionoften requires acute hospitalization and emergency room visits. Amongthose that develop pneumonia due to aspiration, the differentialdiagnosis of ‘aspiration pneumonia’ is not necessarily indicated as aresult of current care practices. Based on U.S. healthcare utilizationsurveys from recent years, pneumonia accounted for over one millionhospital discharges and an additional 392,000 were attributable toaspiration pneumonia. Individuals who have general pneumonia as theprincipal diagnosis have a mean 6 day hospital length of stay and incurover $18,000 in costs for hospital care. It is expected that aspirationpneumonia would carry higher costs for hospital care, based on a mean 8day length of hospital stay. Pneumonia is life threatening among personswith dysphagia, the odds of death within 3 months is about 50% (van derSteen et al. 2002). In addition, an acute insult such as pneumonia ofteninitiates the downward spiral in health among elderly. An insult isassociated with poor intakes and inactivity, resulting in malnutrition,functional decline, and frailty. Specific interventions (e.g., topromote oral health, help restore normal swallow, or reinforce aswallow-safe bolus) would benefit persons at risk for (due to aspirationof oropharyngeal contents, including silent aspiration) or experiencingrecurrent pneumonia.

Similar to pneumonia, dehydration is a life-threatening clinicalcomplication of dysphagia. Dehydration is a common co-morbidity amonghospitalized individuals with neurodegenerative diseases (thus, likelyto have a swallowing impairment). The conditions of Alzheimer's disease,Parkinson's disease, and multiple sclerosis account for nearly 400,000U.S. hospital discharges annually, and up to 15% of these patientssuffer dehydration. Having dehydration as the principal diagnosis isassociated with a mean 4 day length of hospital stay and over $11,000 incosts for hospital care. Nevertheless, dehydration is an avoidableclinical complication of dysphagia.

Malnutrition and related complications (e.g., [urinary tract]infections, pressure ulcers, increased severity of dysphagia [need formore-restricted food options, tube feeding, and/or PEG placement andreduced quality of life], dehydration, functional decline and relatedconsequences [falls, dementia, frailty, loss of mobility, and loss ofautonomy]) can arise when swallowing impairment leads to fear of chokingon food and liquids, slowed rate of consumption, and self-limited foodchoices. If uncorrected, inadequate nutritional intake exacerbatesdysphagia as the muscles that help facilitate normal swallow weaken asphysiological reserves are depleted. Malnutrition is associated withhaving a more than 3-times greater risk of infection. Infections arecommon in individuals with neurodegenerative diseases (thus, likely tohave a chronic swallowing impairment that jeopardizes dietary adequacy).The conditions of Alzheimer's disease, Parkinson's disease, and multiplesclerosis account for nearly 400,000 U.S. hospital discharges annually,and up to 32% of these patients suffer urinary tract infection.

Malnutrition has serious implications for patient recovery. Malnourishedpatients have longer length of hospital stay, are more likely to bere-hospitalized, and have higher costs for hospital care. Havingmalnutrition as the principal diagnosis is associated with a mean 8 daylength of hospital stay and nearly $22,000 in costs for hospital care.Furthermore, malnutrition leads to unintentional loss of weight andpredominant loss of muscle and strength, ultimately impairing mobilityand the ability to care for oneself. With the loss of functionality,caregiver burden becomes generally more severe, necessitating informalcaregivers, then formal caregivers, and then institutionalization.However, malnutrition is an avoidable clinical complication ofdysphagia.

Among persons with neurodegenerative conditions (e.g., Alzheimer'sdisease), unintentional weight loss (a marker of malnutrition) precedescognitive decline. In addition, physical activity can help stabilizecognitive health. Thus, it is important to ensure nutritional adequacyamong persons with neurodegenerative conditions to help them have thestrength and endurance to participate in regular therapeutic exerciseand guard against unintentional weight loss, muscle wasting, loss ofphysical and cognitive functionality, frailty, dementia, and progressiveincrease in caregiver burden.

Falls and related injuries are a special concern among elderly withneurodegenerative conditions, associated with loss of functionality.Falls are the leading cause of injury deaths among older adults.Furthermore, fall-related injuries among elderly accounted for more than1.8M U.S. emergency room visits in a recent year. Direct medical coststotaled $179M for fatal and $19.3B for nonfatal fall-related injuries inthe period of a year. As an effect of an ambitious non-payment forperformance initiative introduced in U.S. hospitals in October 2008,Medicare will no longer pay hospitals for treatment cost of falls andrelated injuries that occur during the hospital stay. Hospitals willface a loss of about $50,000 for each elderly patient who falls andsuffers hip fracture while in hospital care. This new quality initiativeis based on the premise that falls are an avoidable medical error. Inother words, falls are preventable within reason by applyingevidence-based practices including medical nutrition therapy asnutritional interventions are efficacious in the prevention of falls andrelated injuries (e.g., fractures) among elderly.

Chewing and swallowing difficulties are also recognized risk factors forpressure ulcer development. Pressure ulcers are considered an avoidablemedical error, preventable within reason by applying evidence-basedpractices (including nutritional care, as pressure ulcers are morelikely when nutrition is inadequate). Pressure ulcers are a significantburden to the health care system. In U.S. hospitals in 2006, there were322,946 cases of medical error connected with pressure ulcerdevelopment.

The average cost of healing pressure ulcers depends on the stage,ranging from about $1,100 (for stage II) to about $10,000 (for stage III& IV pressure ulcers). Thus, the estimated cost of healing the cases ofmedical error connected with pressure ulcer development in one year, isin the range of $323M to $3.2B. As an effect of an ambitious non-paymentfor performance initiative introduced in U.S. hospitals in October 2008,Medicare will no longer pay hospitals for treatment cost of pressureulcers that develop during the hospital stay (up to $3.2B annually).Pressure ulcers are preventable within reason, in part, by assuringnutritional intakes are adequate. Furthermore, specific interventionsincluding the use of specialized nutritional supplements help reduce theexpected time to heal pressure ulcers once they've developed.

In U.S. long-term care facilities, quality of care standards areenforced via the frequent regulatory survey. Surveyors will considerfacilities out of compliance when they uncover evidence of actual orpotential harm/negative outcomes. The range of penalties include fines,forced closure, as well as lawsuits and settlement fees. The Tag F325(nutrition) survey considers significant unplanned weight change,inadequate food/fluid intake, impairment of anticipated wound healing,failure to provide a therapeutic diet as ordered, functional decline,and fluid/electrolyte imbalance as evidence for providing sub-standard[Nutrition] care. The Tag F314 (pressure ulcers) survey mandates thatthe facility must ensure that a resident who is admitted withoutpressure ulcers does not develop pressure ulcers unless deemedunavoidable. In addition, that a resident having pressure ulcersreceives necessary treatment and services to promote healing, preventinfection and prevent new pressure ulcers from developing.

Considering the prevalence of dysphagia, possible complications relatedthereto, and the costs associated with same, it would be beneficial toprovide nutritional products that promote safer swallowing of foodboluses in patients suffering from such swallowing disorders. Suchnutritional products would improve the lives of a large and growingnumber of persons with swallowing impairments. Specific interventions(e.g., to promote oral health, help restore normal swallow, or reinforcea swallow-safe bolus) can enable persons to eat orally (vs. being tubefed and/or requiring PEG placement) and experience the psycho-socialaspects of food associated with general well being while guardingagainst the potentially negative consequences that result from lack ofadequate swallowing ability. Improvements in the intake of nutrition bydysphagic patients may also enable such patients to swallow a widervariety of food and beverage products safely and comfortably, which maylead to an overall healthier condition of the patient and preventfurther health-related decline.

Several prior art documents disclose compositions for use in dysphagiatreatments, none of which however provides sufficiently viscousproperties to efficiently promote safer swallowing of food boluses.

Chan et al. (see Food Hydrocolloids 21, p. 716-725 (2007)), for example,presents a study of the shear and extensional rheology of casein, waxymaize starch and their mixtures for industrial biopolymers. In thisarticle, Chan et al. mention that the shear and uniaxial extensionalflow behaviour of aqueous casein and phosphate waxy maize starch systemswas measured as a function of the deformation rate, biopolymerconcentration and the temperature. However, Chan et al. do not provideany further applications such as treatment of dysphagia or details as towhich properties a suitable composition shall have to effectivelypromote safer swallowing.

US 2011/217442 (filed on 8 Mar. 2010 by CP Kelco US) mentionscompositions and methods for producing consumables for patients withdysphagia. In this context, US 2011/217442 mentions compositionsincluding a modified xanthan gum in an amount suitable to provide aviscous, free-flowing solution having gel-like properties. US2011/217442 does not provide any further components or information onspecific viscosities suitable to promote safer swallowing.

WO 2011/056487 (filed on 25 Oct. 2010 by Nestec S.A) deals with stablethickener formulations and nutritional compositions comprising such astable thickener formulation, e.g. a stable thickener formulationcomprising from about 0.015 percent to about 0.05 percent by weight ofcarrageenan and from about 1.2 percent to about 4.0 percent by weight ofstarch. The stable thickener formulation can be used in nutritionalcompositions used to treat a variety of physiological conditions. WO2011/056487 does not provide any further components or rheologicalrequirements suitable to promote safer swallowing.

In view of the prior art, there remains a need to provide improvednutritional products which promote safer swallowing of food boluses andmethods for administering same to patients having swallowing conditionsor being impaired thereby.

SUMMARY

The present disclosure is related to nutritional products and methodsfor administering same. More specifically, the present disclosure isrelated to nutritional products for promoting safer swallowing of foodboluses. In a general embodiment, a nutritional product including anutritional composition and a food grade polymer capable of increasingan extensional viscosity of the composition such that the nutritionalproduct has a Trouton ratio that is at least 6, preferably from about 6to about 15. In an embodiment, the Trouton ratio is about 10. In anotherembodiment, the inventive nutritional product has an extensionalviscosity that is greater than 100 milli Pascal seconds (“mPas”).

In an embodiment, the food grade polymer is selected from the groupconsisting of plant-extracted gums, plant-derived mucilages andcombinations thereof. The plant-extracted gums may further be selectedfrom the group consisting of okra gum, konjac mannan, tara gum, locustbean gum, guar gum, fenugreek gum, tamarind gum, cassia gum, acacia gum,gum ghatti, pectins, cellulosics, tragacanth gum, karaya gum, or anycombinations thereof, In a preferred embodiment, the plant-extracted gumis okra gum. Further, the plant-derived mucilages may be selected fromthe group consisting of cactus mucilage (Ficus indica), psylliummucilage (Plantago ovata), mallow mucilage (Malva sylvestris), flax seedmucilage (Linum usitatissimum), marshmallow mucilage (Althaeaofficinalis), ribwort mucilage (Plantago lanceolata), mullein mucilage(Verbascum), cetraria mucilage (Lichen islandicus), or any combinationsthereof. In a preferred embodiment, the plant-derived mucilage is cactusmucilage (Ficus indica). It is particularly preferred that the foodgrade polymer is selected from okra gum and/or cactus mucilage (Ficusindica), or a combination thereof. In a further preferred embodiment,the plant-extracted gums and/or the inventive nutritional product do notcontain starch, such as waxy maize starch, xanthan gum, modified xanthangum such as non-pyruvylated xanthan gum or reduced-pyruvylated xanthangum, carageenan, or a combination thereof. Preferably, it does notcontain a combination of starch and carrageenan or a combination ofcasein and waxy maize starch.

In an embodiment, the inventive nutritional products include aprebiotic. The prebiotic is selected from the group consisting offructooligosaccharides, inulin, lactulose, galactooligosaccharides,acacia gum, soyoligosaccharides, xylooligosaccharides,isomaltooligosaccharides, gentiooligosaccharides, lactosucrose,glucooligosaccharides, pecticoligosaccharides, resistant starches, sugaralcohols or combinations thereof.

In an embodiment, the inventive nutritional products include aprobiotic. The probiotic is selected from the group consisting ofSaccharomyces, Debaromyces, Candida, Pichia, Torulopsis, Aspergillus,Rhizopus, Mucor, Penicillium, Torulopsis, Bifidobacterium, Bacteroides,Clostridium, Fusobacterium, Melissococcus, Propionibacterium,Streptococcus, Enterococcus, Lactococcus, Staphylococcus,Peptostrepococcus, Bacillus, Pediococcus, Micrococcus, Leuconostoc,Weissella, Aerococcus, Oenococcus, Lactobacillus or combinationsthereof.

In an embodiment, the inventive nutritional products include an aminoacid. The amino acid is selected from the group consisting ofIsoleucine, Alanine, Leucine, Asparagine, Lysine, Aspartate, Methionine,Cysteine, Phenylalanine, Glutamate, Threonine, Glutamine, Tryptophan,Citrulline, Glycine, Valine, Proline, Serine, Tyrosine, Arginine,Histidine or combinations thereof.

In an embodiment, the inventive nutritional product includes a fattyacid component of a fish oil selected from the group consisting ofdocosahexaenoic acid (“DHA”), eicosapentaenoic acid (“EPA”), orcombinations thereof. DHA and EPA may also be derived from krill, algae,modified plants, flaxseed, walnut, etc. Certain fatty acids (e.g., 18:4fatty acids) may also be readily converted to DHA and/or EPA. Thenutritional product may further include α-linolenic acid.

In an embodiment, the inventive nutritional products include aphytonutrient. The phytonutrient is selected from the group consistingof quercetin, curcumin, limonin or combinations thereof.

In an embodiment, the inventive nutritional products include anantioxidant. The antioxidant is selected from the group consisting ofvitamin A, carotenoids, vitamin C, vitamin E, selenium, flavonoids,Lactowolfberry, wolfberry, polyphenols, lycopene, lutein, lignan,coenzyme Q10, glutathione or combinations thereof.

In an embodiment, the inventive nutritional product is in anadministrable form selected from the group consisting of pharmaceuticalformulations, nutritional formulations, dietary supplements, functionalfood and beverage products or combinations thereof. The inventivenutritional product may be present in a liquid, a semi-liquid or asemi-solid state. Alternatively, the nutritional product as definedherein may be provided in dry form, such as a powder, wherein, uponadding water or an appropriate liquid as defined herein, the nutritionalproduct as defined herein can be reconstituted to exhibit a Troutonratio that is at least 6, and that is preferably from about 6 to about15.

In yet another embodiment, methods for making a nutritional product areprovided. The methods include providing a nutritional composition andadding a food grade polymer to the nutritional composition to form anutritional product having a Trouton ratio that is at least 6, and thatis preferably from about 6 to about 15. In an embodiment, the Troutonratio may be about 10. In another embodiment, the nutritional productmay have an extensional viscosity that is greater than 100 milli Pascalseconds (“mPas”). Preferably, the nutritional product is as definedherein.

In still yet another embodiment, methods for improving the cohesivenessof a nutritional product are provided. The methods include adding to anutritional composition a food grade polymer to form a nutritionalproduct, preferably as defined herein, the food grade polymer capable ofimproving a cohesiveness of the nutritional composition such that thenutritional product does not break-up during consumption of thenutritional product. In an embodiment, a Trouton ratio of thenutritional product is at least 6, and preferably from about 6 to about15. In a particularly preferred embodiment, the Trouton ratio may beabout 10. In another embodiment, the nutritional product may have anextensional viscosity that is greater than 100 milli Pascal seconds(“mPas”).

In still yet another embodiment, methods for promoting safe swallowingof food boluses are provided. The methods include adding to anutritional composition a food grade polymer to form a nutritionalproduct, preferably as defined herein, the food grade polymer capable ofimproving a cohesiveness of the nutritional composition such that thenutritional product does not break-up during consumption of thenutritional product, and administering the nutritional product to apatient in need of same. In an embodiment, a Trouton ratio of thenutritional product is at least 6, and preferably from about 6 to about15. In a particularly preferred embodiment, the Trouton ratio may beabout 10. In another embodiment, the nutritional product may have anextensional viscosity that is greater than 100 milli Pascal seconds(“mPas”). The viscosity may be determined using methods known to aperson skilled in the art.

In another embodiment, methods for treating a patient having aswallowing disorder are provided. The methods include administering to apatient in need of same a nutritional product, preferably as definedherein, comprising a nutritional composition and a food grade polymer,the nutritional product having a Trouton ration that is at least 6, andpreferably from about 6 to about 15. In a preferred embodiment, theTrouton ratio may be about 10. In another embodiment, the nutritionalproduct may have an extensional viscosity that is greater than 100 milliPascal seconds (“mPas”).

In an embodiment, the food grade polymer is selected from the groupconsisting of plant-extracted gums, plant-derived mucilages andcombinations thereof. The plant-extracted gums may further be selectedfrom the group consisting of okra gum, konjac mannan, tara gum, locustbean gum, guar gum, fenugreek gum, tamarind gum, cassia gum, acacia gum,gum ghatti, pectins, cellulosics, tragacanth gum, karaya gum, or anycombinations thereof. In a preferred embodiment, the plant-extracted gumis okra gum. The plant-derived mucilages may be selected from the groupconsisting of cactus mucilage (Ficus indica), psyllium mucilage(Plantago ovata), mallow mucilage (Malva sylvestris), flax seed mucilage(Linum usitatissimum), marshmallow mucilage (Althaea officinalis),ribwort mucilage (Plantago lanceolate), mullein mucilage (Verbascum),cetraria mucilage (Lichen islandicus), or any combinations thereof. In apreferred embodiment, the plant-derived mucilage is cactus mucilage(Ficus indica). It is particularly preferred that the food grade polymeris selected from okra gum and/or cactus mucilage (Ficus indica), or acombination thereof. In a further preferred embodiment, theplant-extracted gums and/or the inventive nutritional product do notcontain starch, such as waxy maize starch, xanthan gum, modified xanthangum such as non-pyruvylated xanthan gum or reduced-pyruvylated xanthangum, carageenan, or a combination thereof. Preferably, it does notcontain a combination of starch and carrageenan or a combination ofcasein and waxy maize starch.

An advantage of the present disclosure is to provide improvednutritional products.

Another advantage of the present disclosure is to provide nutritionalproducts having improved cohesiveness.

Yet another advantage of the present disclosure is to provide improvednutritional products for patients having dysphagia.

Still yet another advantage of the present disclosure is to providemethods for treating patients having dysphagia.

Another advantage of the present disclosure is to provide methods forimproving the cohesiveness of a composition.

Yet another advantage of the present disclosure is to provide methodsfor promoting safe swallowing of food boluses.

Additional features and advantages are described herein, and will beapparent from the following detailed description.

DETAILED DESCRIPTION

As used herein, “about” is understood to refer to numbers in a range ofnumerals. Moreover, all numerical ranges herein should be understood toinclude all integer, whole or fractions, within the range.

As used herein the term “amino acid” is understood to include one ormore amino acids. The amino acid can be, for example, alanine, arginine,asparagine, aspartate, citrulline, cysteine, glutamate, glutamine,glycine, histidine, hydroxyproline, hydroxyserine, hydroxytyrosine,hydroxylysine, isoleucine, leucine, lysine, methionine, phenylalanine,proline, serine, taurine, threonine, tryptophan, tyrosine, valine, orcombinations thereof.

As used herein, “animal” includes, but is not limited to, mammals, whichinclude but is not limited to, rodents, aquatic mammals, domesticanimals such as dogs and cats, farm animals such as sheep, pigs, cowsand horses, and humans. Wherein the terms “animal” or “mammal” or theirplurals are used, it is contemplated that it also applies to any animalsthat are capable of the effect exhibited or intended to be exhibited bythe context of the passage.

As used herein, the term “antioxidant” is understood to include any oneor more of various substances such as beta-carotene (a vitamin Aprecursor), vitamin C, vitamin E, and selenium) that inhibit oxidationor reactions promoted by Reactive Oxygen Species (“ROS”) and otherradical and non-radical species. Additionally, antioxidants aremolecules capable of slowing or preventing the oxidation of othermolecules. Non-limiting examples of antioxidants include carotenoids,coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji (wolfberry),hesperidin, lactowolfberry, lignan, lutein, lycopene, polyphenols,selenium, vitamin A, vitamin B1, vitamin B6, vitamin B12, vitamin C,vitamin D, vitamin E, zeaxanthin, or combinations thereof.

As used herein, “effective amount” is an amount that prevents adeficiency, treats a disease or medical condition as mentioned herein inan individual or, more generally, reduces symptoms, manages progressionof the diseases mentioned herein or provides a nutritional,physiological, or medical benefit to the individual. A treatment can bepatient- or doctor-related.

While the terms “individual” and “patient” are often used herein torefer to a human, the invention is not so limited. Accordingly, theterms “individual” and “patient” refer to any animal, mammal or humanhaving or at risk for a medical condition that can benefit from thetreatment. More preferably, the term “patient” as defined herein, isused for an animal, mammal or human, typically suffering from a diseaseas defined herein.

As used herein, non-limiting examples of sources of co-3 fatty acidssuch α-linolenic acid (“ALA”), docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”) include fish oil, krill, poultry, eggs, orother plant or nut sources such as flax seed, walnuts, almonds, algae,modified plants, etc.

As used herein, “food grade micro-organisms” means micro-organisms thatare used and generally regarded as safe for use in food.

As used herein, “mammal” includes, but is not limited to, rodents,aquatic mammals, domestic animals such as dogs and cats, farm animalssuch as sheep, pigs, cows and horses, and humans. Wherein the term“mammal” is used, it is contemplated that it also applies to otheranimals that are capable of the effect exhibited or intended to beexhibited by the mammal.

The term “microorganism” is meant to include the bacterium, yeast and/orfungi, a cell growth medium with the microorganism, or a cell growthmedium in which microorganism was cultivated.

As used herein, the term “minerals” is understood to include boron,calcium, chromium, copper, iodine, iron, magnesium, manganese,molybdenum, nickel, phosphorus, potassium, selenium, silicon, tin,vanadium, zinc, or combinations thereof.

As used herein, a “non-replicating” microorganism means that no viablecells and/or colony forming units can be detected by classical platingmethods. Such classical plating methods are summarized in themicrobiology book: James Monroe Jay, et al., Modern food microbiology,7th edition, Springer Science, New York, N. Y. p. 790 (2005). Typically,the absence of viable cells can be shown as follows: no visible colonyon agar plates or no increasing turbidity in liquid growth medium afterinoculation with different concentrations of bacterial preparations (nonreplicating' samples) and incubation under appropriate conditions(aerobic and/or anaerobic atmosphere for at least 24 h). For example,bifidobacteria such as Bifidobacterium longum, Bifidobacterium lactisand Bifidobacterium breve or lactobacilli, such as Lactobacillusparacasei or Lactobacillus rhamnosus, may be rendered non-replicating byheat treatment, in particular low temperature/long time heat treatment.

As used herein, a “nucleotide” is understood to be a subunit ofdeoxyribonucleic acid (“DNA”) or ribonucleic acid (“RNA”). It is anorganic compound made up of a nitrogenous base, a phosphate molecule,and a sugar molecule (deoxyribose in DNA and ribose in RNA). Individualnucleotide monomers (single units) are linked together to form polymers,or long chains. Exogenous nucleotides are specifically provided bydietary supplementation. The exogenous nucleotide can be in a monomericform such as, for example, 5′-Adenosine Monophosphate (“5′ -AMP”),5′-Guanosine Monophosphate (“5′ -GMP”), 5′ -Cytosine Monophosphate(“5′-CMP”), 5′ -Uracil Monophosphate (“5′-UMP”), 5′ -InosineMonophosphate (“51-IMP”), 5′-Thymine Monophosphate (“5′-TMP”), orcombinations thereof. The exogenous nucleotide can also be in apolymeric form such as, for example, an intact RNA. There can bemultiple sources of the polymeric form such as, for example, yeast RNA.

“Nutritional compositions,” as used herein, are understood to includeany number of optional additional ingredients, including conventionalfood additives, for example one or more, acidulants, additionalthickeners, buffers or agents for pH adjustment, chelating agents,colorants, emulsifies, excipient, flavor agent, mineral, osmotic agents,a pharmaceutically acceptable carrier, preservatives, stabilizers,sugar, sweeteners, texturizers, and/or vitamins. The optionalingredients can be added in any suitable amount.

As used herein the term “patient” is understood to include an animal,especially a mammal, and more especially a human that is receiving orintended to receive treatment, as it is herein defined. A patient may begenerally of any age, e.g. a young patient (e.g. between about 0 and 30years), a medium aged patient (e.g. between about 30 and 50 years) or anelderly patient. More preferably, a patient is an elderly patient,preferably an elderly mammal or human patient, more preferably a humanover 50 years of age, even more preferably a human over 60 years of ageand most preferably a human over 70 years of age, receiving or intendedto receive a treatment, preferably against a disease as defined herein.

As used herein, “phytochemicals” or “phytonutrients” are non-nutritivecompounds that are found in many foods. Phytochemicals are functionalfoods that have health benefits beyond basic nutrition, and are healthpromoting compounds that come from plant sources. “Phytochemicals” and“Phytonutrients” refers to any chemical produced by a plant that impartsone or more health benefit on the user. Non-limiting examples ofphytochemicals and phytonutrients include those that are:

i) phenolic compounds which include monophenols (such as, for example,apiole, carnosol, carvacrol, dillapiole, rosemarinol); flavonoids(polyphenols) including flavonols (such as, for example, quercetin,fingerol, kaempferol, myricetin, rutin, isorhamnetin), flavanones (suchas, for example, fesperidin, naringenin, silybin, eriodictyol), flavones(such as, for example, apigenin, tangeritin, luteolin), flavan-3-ols(such as, for example, catechins, (+)-catechin, (+)-gallocatechin,(−)-epicatechin, (−)-epigallocatechin, (−)-epigallocatechin gallate(EGCG), (−)-epicatechin 3-gallate, theaflavin, theaflavin-3 -gallate,theaflavin-3′-gallate, theaflavin-3,3′-digallate, thearubigins),anthocyanins (flavonals) and anthocyanidins (such as, for example,pelargonidin, peonidin, cyanidin, delphinidin, malvidin, petunidin),isoflavones (phytoestrogens) (such as, for example, daidzein(formononetin), genistein (biochanin A), glycitein), dihydroflavonols,chalcones, coumestans (phytoestrogens), and Coumestrol; Phenolic acids(such as: Ellagic acid, Gallic acid, Tannic acid, Vanillin, curcumin);hydroxycinnamic acids (such as, for example, caffeic acid, chlorogenicacid, cinnamic acid, ferulic acid, coumarin); lignans (phytoestrogens),silymarin, secoisolariciresinol, pinoresinol and lariciresinol); tyrosolesters (such as, for example, tyrosol, hydroxytyrosol, oleocanthal,oleuropein); stilbenoids (such as, for example, resveratrol,pterostilbene, piceatannol) and punicalagins;

ii) terpenes (isoprenoids) which include carotenoids (tetraterpenoids)including carotenes (such as, for example, a-carotene, n-carotene,7-carotene, 0.5-carotene, lycopene, neurosporene, phytofluene,phytoene), and xanthophylls (such as, for example, canthaxanthin,cryptoxanthin, aeaxanthin, astaxanthin, lutein, rubixanthin);monoterpenes (such as, for example, limonene, perillyl alcohol);saponins; lipids including: phytosterols (such as, for example,campesterol, beta sitosterol, gamma sitosterol, stigmasterol),tocopherols (vitamin E), and co-3, -6, and -9 fatty acids (such as, forexample, gamma-linolenic acid); triterpenoid (such as, for example,oleanolic acid, ursolic acid, betulinic acid, moronic acid);

iii) betalains which include Betacyanins (such as: betanin, isobetanin,probetanin, neobetanin); and betaxanthins (non glycosidic versions)(such as, for example, indicaxanthin, and vulgaxanthin);

iv) organosulfi des, which include, for example, dithiolthiones(isothiocyanates) (such as, for example, sulphoraphane); andthiosulphonates (allium compounds) (such as, for example, allyl methyltrisulfide, and diallyl sulfide), indoles, glucosinolates, whichinclude, for example, indole-3-carbinol; sulforaphane;3,3′-diindolylmethane; sinigrin; allicin; alliin; allyl isothiocyanate;piperine; syn-propanethial-S-oxide;

v) protein inhibitors, which include, for example, protease inhibitors;

vi) other organic acids which include oxalic acid, phytic acid (inositolhexaphosphate); tartaric acid; and anacardic acid; or

vii) combinations thereof.

As used in this disclosure and the appended claims, the singular forms“a,” “an” and “the” include plural referents unless the context clearlydictates otherwise. Thus, for example, reference to “a polypeptide”includes a mixture of two or more polypeptides, and the like.

As used herein, a “prebiotic” is a food substance that selectivelypromotes the growth of beneficial bacteria or inhibits the growth ormucosal adhesion of pathogenic bacteria in the intestines. They are notinactivated in the stomach and/or upper intestine or absorbed in thegastrointestinal tract of the person ingesting them, but they arefermented by the gastrointestinal microflora and/or by probiotics.Prebiotics are, for example, defined by Glenn R. Gibson and Marcel B.Roberfroid, Dietary Modulation of the Human Colonic Microbiota:Introducing the Concept of Prebiotics, J. Nutr. 1995 125: 1401-1412.Non-limiting examples of prebiotics include acacia gum, alpha glucan,arabinogalactans, beta glucan, dextrans, fructooligosaccharides,fucosyllactose, galactooligosaccharides, galactomannans,gentiooligosaccharides, glucooligosaccharides, guar gum, inulin,isomaltooligosaccharides, lactoneotetraose, lactosucrose, lactulose,levan, maltodextrins, milk oligosaccharides, partially hydrolyzed guargum, pecticoligosaccharides, resistant starches, retrograded starch,sialooligosaccharides, sialyllactose, soyoligosaccharides, sugaralcohols, xylooligosaccharides, or their hydrolysates, or combinationsthereof.

As used herein, probiotic micro-organisms (hereinafter “probiotics”) arefood-grade microorganisms (alive, including semi-viable or weakened,and/or non-replicating), metabolites, microbial cell preparations orcomponents of microbial cells that could confer health benefits on thehost when administered in adequate amounts, more specifically, thatbeneficially affect a host by improving its intestinal microbialbalance, leading to effects on the health or well-being of the host.See, Salminen S, Ouwehand A. Benno Y. et al., Probiotics: how shouldthey be defined?, Trends Food Sci. Technol. 1999:10, 107-10. In general,it is believed that these micro-organisms inhibit or influence thegrowth and/or metabolism of pathogenic bacteria in the intestinal tract.The probiotics may also activate the immune function of the host. Forthis reason, there have been many different approaches to includeprobiotics into food products. Non-limiting examples of probioticsinclude Aerococcus, Aspergillus, Bacillus, Bacteroides, Bifidobacterium,Candida, Clostridium, Debaromyces, Enterococcus, Fusobacterium,Lactobacillus, Lactococcus, Leuconostoc, Melissococcus, Micrococcus,Mucor, Oenococcus, Pediococcus, Penicillium, Peptostrepococcus, Pichia,Propionibacterium, Pseudocatenulatum, Rhizopus, Saccharomyces,Staphylococcus, Streptococcus, Torulopsis, Weissella, or combinationsthereof.

The terms “protein,” “peptide,” “oligopeptides” or “polypeptide,” asused herein, are understood to refer to any composition that includes, asingle amino acids (monomers), two or more amino acids joined togetherby a peptide bond (dipeptide, tripeptide, or polypeptide), collagen,precursor, homolog, analog, mimetic, salt, prodrug, metabolite, orfragment thereof or combinations thereof. For the sake of clarity, theuse of any of the above terms is interchangeable unless otherwisespecified. It will be appreciated that polypeptides (or peptides orproteins or oligopeptides) often contain amino acids other than the 20amino acids commonly referred to as the 20 naturally occurring aminoacids, and that many amino acids, including the terminal amino acids,may be modified in a given polypeptide, either by natural processes suchas glycosylation and other post-translational modifications, or bychemical modification techniques which are well known in the art. Amongthe known modifications which may be present in polypeptides of thepresent invention include, but are not limited to, acetylation,acylation, ADP-ribosylation, amidation, covalent attachment of aflavanoid or a heme moiety, covalent attachment of a polynucleotide orpolynucleotide derivative, covalent attachment of a lipid or lipidderivative, covalent attachment of phosphatidylinositol, cross-linking,cyclization, disulfide bond formation, demethylation, formation ofcovalent cross-links, formation of cystine, formation of pyroglutamate,formylation, gamma-carboxylation, glycation, glycosylation,glycosylphosphatidyl inositol (“GPI”) membrane anchor formation,hydroxylation, iodination, methylation, myristoylation, oxidation,proteolytic processing, phosphorylation, prenylation, racemization,selenoylation, sulfation, transfer-RNA mediated addition of amino acidsto polypeptides such as arginylation, and ubiquitination. The term“protein” also includes “artificial proteins” which refers to linear ornon-linear polypeptides, consisting of alternating repeats of a peptide.

Non-limiting examples of proteins include dairy based proteins, plantbased proteins, animal based proteins and artificial proteins. Dairybased proteins include, for example, casein, caseinates (e.g., all formsincluding sodium, calcium, potassium caseinates), casein hydrolysates,whey (e.g., all forms including concentrate, isolate, demineralized),whey hydrolysates, milk protein concentrate, and milk protein isolate.Plant based proteins include, for example, soy protein (e.g., all formsincluding concentrate and isolate), pea protein (e.g., all formsincluding concentrate and isolate), canola protein (e.g., all formsincluding concentrate and isolate), other plant proteins thatcommercially are wheat and fractionated wheat proteins, corn and itfractions including zein, rice, oat, potato, peanut, green pea powder,green bean powder, and any proteins derived from beans, lentils, andpulses. Animal based proteins may be selected from the group consistingof beef, poultry, fish, lamb, seafood, or combinations thereof.

All dosage ranges contained within this application are intended toinclude all numbers, whole or fractions, contained within said range.

As used herein, a “synbiotic” is a supplement that contains both aprebiotic and a probiotic that work together to improve the microfloraof the intestine.

As used herein, the terms “treatment,” “treat” and “to alleviate”include both prophylactic or preventive treatment (that prevent and/orslow the development of a targeted pathologic condition or disorder) andcurative, therapeutic or disease-modifying treatment, includingtherapeutic measures that cure, slow down, lessen symptoms of, and/orhalt progression of a diagnosed pathologic condition or disorder; andtreatment of patients at risk of contracting a disease or suspected tohave contracted a disease, as well as patients who are ill or have beendiagnosed as suffering from a disease or medical condition. The termdoes not necessarily imply that a subject is treated until totalrecovery. The terms “treatment” and “treat” also refer to themaintenance and/or promotion of health in an individual not sufferingfrom a disease but who may be susceptible to the development of anunhealthy condition, such as nitrogen imbalance or muscle loss. Theterms “treatment,” “treat” and “to alleviate” are also intended toinclude the potentiation or otherwise enhancement of one or more primaryprophylactic or therapeutic measure. The terms “treatment,” “treat” and“to alleviate” are further intended to include the dietary management ofa disease or condition or the dietary management for prophylaxis orprevention a disease or condition. More preferably, the term “treatment”in the context of the present invention refers to prevention and/ortreatment of swallowing disorders, preferably prevention and/ortreatment of dysphagia, but also prevention and/or treatment ofmalnourishment or undernourishment associated with dysphagia, preferablyas mentioned above, such as e.g. silent aspiration, pneumonia,aspiration pneumonia, dehydration, pressure ulcers, etc. Treatment alsomay be accomplished with regard to dysphagia patients or patients highlysusceptible of dysphagia or at risk of developing dysphagia, such aspatients suffering from stroke, Parkinson's, Alzheimer's, Brain Damageand Multiple Sclerosis.

As used herein the term “vitamin” is understood to include any ofvarious fat-soluble or water-soluble organic substances (non-limitingexamples include vitamin A, Vitamin B1 (thiamine), Vitamin B2(riboflavin), Vitamin B3 (niacin or niacinamide), Vitamin B5(pantothenic acid), Vitamin B6 (pyridoxine, pyridoxal, or pyridoxamine,or pyridoxine hydrochloride), Vitamin B7 (biotin), Vitamin B9 (folicacid), and Vitamin B12 (various cobalamins; commonly cyanocobalamin invitamin supplements), vitamin C, vitamin D, vitamin E, vitamin K, folicacid and biotin) essential in minute amounts for normal growth andactivity of the body and obtained naturally from plant and animal foodsor synthetically made, pro-vitamins, derivatives, analogs.

The present disclosure relates to nutritional products for promotingsafer swallowing of food boluses for patients suffering from swallowingdisorders including, for example, dysphagia. The present disclosure alsorelates to methods for providing treatment for a patient having aswallowing disorder.

The normal swallowing of a human (or mammal) involves three distinctphases which are interdependent and well coordinated: (i) the oral, (ii)the pharyngeal, and (iii) the esophageal phases. In the oral phase,which is under voluntary control, food that has been chewed and mixedwith saliva is formed into a bolus for delivery by voluntary tonguemovements to the back of the mouth, into the pharynx. The pharyngealphase is involuntary and is triggered by food/liquid bolus passingthrough the faucial pillars into the pharynx. Contraction of the threeconstrictors of the pharynx propel the bolus towards the upperesophageal sphincter. Simultaneously, the soft palate closes thenasopharynx. The larynx moves upwards to prevent food or liquid passinginto the airway, which is aided by the backward tilt of the epiglottisand closure of the vocal folds. The esophageal phase is also involuntaryand starts with the relaxation of the upper esophageal sphincterfollowed by peristalsis, which pushes the bolus down to the stomach.

Dysphagia refers to the symptom of difficulty in swallowing. Thefollowing general causes of dysphagia have been identified:

a) A decreased ability to swallow

b) Tongue not exerting enough pressure on soft palate

i) Iatrogenic

(1) Surgical removal of part of the tongue or soft palate

(a) Treatment for snoring or sleep apnea

(b) Resection due to tumor (malignant or benign)

ii) Genetic

(1) Hypoplasia of the tongue and/or soft palate

(2) Hypo or lack of innervation to tongue and/or soft palate

iii) Traumatic

(1) Tissue damage

(2) Deinnervation/hypoinnervation

iv) Neurologic

(1) Local deinnervation/hypoinnervation

(2) CNS

(a) Post stroke

(b) Demylination

c) Abnormal epiglottis behavior

i) Not closing and opening at proper times

(1) Opening too early

(2) Not closing in time

(a) Delayed closing

ii) Not closing completely (insufficient flexibility—atrophy)

The consequences of untreated or poorly managed oral pharyngealdysphagia can be severe, including dehydration, malnutrition leading todysfunctional immune response, and reduced functionality, airwayobstruction with solid foods (choking), and airway aspiration of liquidsand semi-solid foods, promoting aspiration pneumonia and/or pneumonitis.Severe oral pharyngeal dysphagia may require nutrition to be supplied bytube feeding.

Mild to moderate oral pharyngeal dysphagia may require the texture offoods to be modified in order to minimize the likelihood of choking oraspiration. This may include the thickening of liquids and/or pureeingof solid foods, both of which have been shown to be the most effectivemeans of preventing choking and aspiration during the eating process.Thickened liquids are designed to have three properties: (i) a morecohesive bolus that can be maintained throughout the action ofswallowing, (ii) slower delivery to the throat, thereby compensating forthe increased period in which the swallowing reflexes prepare for thethickened liquid, and (iii) provide greater density to increaseawareness of the presence of food or liquid bolus in the mouth.

Improving an individual's ability and efficiency to swallow improves theindividual's safety through reduced risk of pulmonary aspiration. Anefficient swallow may permit greater independence from feedingassistance and/or reduced length of time spent in feeding-assistanceduring meal consumption. Efficient swallowing also reduces the viscosityof liquids required for safety (e.g., pudding, honey and nectarthickness products) and may also limit the use of texture-modifiedfoods. All of these previously described factors are aimed at improvingan individual's quality of life.

In a general embodiment, the present disclosure provides nutritionalproducts for promoting safer swallowing of food boluses in patients withswallowing disorders (e.g., dysphagic patients) by preventing boluspenetration and aspiration through modification of rheologicalproperties of foods and beverages. Rheology is the study of the flow ofmatter, primarily in the liquid state but also as soft solids or solidsunder conditions in which they respond with plastic flow rather thandeforming elastically in response to an applied force. The flow ofsubstances cannot generally be characterized by a single value ofviscosity, although viscosity measurements at specific temperatures canprovide valuable information about a material's properties. Rheologicalstudies are generally performed using rheometers, which generally imposea specific stress field or deformation to the fluid and monitor theresultant deformation or stress. These instruments may operate in steadyflow or oscillatory flow, as well as both shear and extension.

A commonly measured rheological property of a material is its shearviscosity. Shear viscosity, often referred to as simply viscosity,describes the reaction of a material to applied shear stress. In otherwords, shear stress is the ratio between “stress” (force per unit area)exerted on the surface of a fluid, in the lateral or horizontaldirection, to the change in velocity of the fluid as you move down inthe fluid (a “velocity gradient”). Volume viscosity or bulk viscosity,describes the reaction to compression and is essential forcharacterization of acoustics in fluids. Viscosity is preferablymeasured using methods known to a person skilled in the art.

Another rheological property of a material is its extensional viscosity.Extensional viscosity is the ratio of the stress required to extend aliquid in its flow direction to the extension rate. Extensionalviscosity coefficients are widely used for characterizing polymers,where they cannot be simply calculated or estimated from the shearviscosity.

During processing in the mouth and swallowing, the viscosity of a foodproduct changes due to shear forces. It is generally known that theviscosity of a food product decreases when the shear forces and rateacting on the food product (e.g., chewing forces) increase. A knowtreatment for beverages and liquid foods is to increase the viscosity ofthe food/beverage by adding starch or gum thickeners. Such thickening isthought to improve bolus control and timing of swallowing. It is,however, often disliked by patients because of the extra swallowingeffort and may also leave residues at high levels of viscosity. Forsolid foods, pureed diets are often described when problems withmastication and swallowing of solid pieces occur in patients. However,these pureed diets may lack the natural cohesiveness that salivaprovides to “real” food boluses.

Extensional viscosity is generally only relevant in flows where a fluidis “stretched”/extended (e.g., when a flowing through a constrictionsuch as an esophageal sphincter), or when compressed (e.g., between thetongue and plate or the tongue and pharynx). However, any compressiveforce also implies an extension (e.g., in another direction). Only inso-called “simple shear” flows, like in a straight pipe would the shearviscosity alone determine the fluid flow. In a process like swallowing,most steps of the bolus transport will have a certain degree ofextension as well. The difference between shear and extensionalviscosity is usually expressed in terms of a “Trouton ratio,” which isthe ratio between the extensional viscosity and the shear viscosity atthe same rate of deformation and as expressed in reciprocal seconds.Because of the presence of both shear and extensional forces, Applicantshave found that it is important to consider the extensional viscosityand Trouton ratio of nutritional products for patients having difficultyswallowing.

As such and as opposed to the effects of shear viscosity, thenutritional products of the present disclosure aim to improve thecohesion of food boluses to prevent a food bolus from being broken upinto smaller fragments, which may enter the airway or leave unwantedresidues in the oropharyngeal and/or esophageal tract during theswallowing process. Salivary proteins appear to naturally have thisfunction of increasing the cohesiveness of a food bolus. Applicants havesurprisingly found that the incorporation of food grade polymers innutritional products achieves a similar or identical, possibly evenenhanced effect of increasing the cohesiveness of the food bolus (e.g.,for patients who have compromised secretion of saliva). This principlemay be applicable both to beverages, in which such polymers may bedissolved, and semi-solid foodstuffs (e.g., purees) which need tomaintain sufficient integrity to be safely swallowed and where solid andsemi-solid particles are held together by a “cohesive” aqueous phasecontaining such polymers.

Applicants have also found that providing inventive nutritional productsto dysphagic patients having increased bolus cohesion due to itsextensional viscosity, without dramatically modifying other physicalproperties of the material such as, for example, its shear viscosity,dramatically reduces the amount of swallowing effort for the patient, aswell as the risk of residue build-up in the oropharyngeal and/oresophageal tracts. As such, products having increased cohesivenessprovide improved nutritional intake of dysphagic patients by enablingthem to swallow a wider variety of food and beverage products safely andcomfortably. This is achieved by improving bolus integrity(“cohesiveness”) and thus lending confidence to the patient in beingable to consume the different products. The nutritional improvementachieved by an improved food and water intake may lead to an overallhealthier condition of the patient and prevent further decline.

The polymers included in the present nutritional products may includehigh molecular weight, water-soluble polymers that are capable ofenhancing the extensional viscosity and, thus, the cohesiveness (e.g.,resistance to break-up) of the nutritional products. Such polymersinclude, for example, plant-extracted gums, gums produced by bacteria,high molecular weight proteins, synthetic polymers, plant-derivedmucilages and chemically modified biopolymers. It is particularlypreferred that plant-extracted gums and/or plant-derived mucilages areincluded in the present nutritional product and are as defined herein.

Thus, gums that may be used in the present nutritional products mayinclude, for example, xanthan gum, glucomannans (konjac mannan),galactomannans (tara gum, locust bean gum, guar gum, fenugreek gum),dextran, gellan gum, tamarind gum, cassia gum, gum Arabic (acacia gum),gum ghatti, pectin, cellulosics, agar, carrageenan, alginate, tragacanthgum, karaya gum, curdlan gum, okra gum, or combinations thereof. In anembodiment, the food grade polymer is selected from the group consistingof plant-extracted gums, plant-derived mucilages and combinationsthereof. The plant-extracted gums may further be selected from the groupconsisting of okra gum, konjac mannan, tara gum, locust bean gum, guargum, fenugreek gum, tamarind gum, cassia gum, acacia gum, gum ghatti,pectins, cellulosics, tragacanth gum, karaya gum, or any combinationsthereof. In a preferred embodiment, the plant-extracted gum is okra gum.The plant-derived mucilages may be selected from the group consisting ofcactus mucilage (Ficus indica), psyllium mucilage (Plantago ovata), mallow mucilage (Malva sylvestris), flax seed mucilage (Linumusitatissimum), marshmallow mucilage (Althaea officinalis), ribwortmucilage (Plantago lanceolata), mullein mucilage (Verbascum), cetrariamucilage (Lichen islandicus), or any combinations thereof. In apreferred embodiment, the plant-derived mucilage is cactus mucilage(Ficus indica). It is particularly preferred that the food grade polymeris selected from okra gum and/or cactus mucilage (Ficus indica), or acombination thereof. In a further preferred embodiment, theplant-extracted gums and/or the inventive nutritional product do notcontain starch, such as waxy maize starch, xanthan gum, modified xanthangum such as non-pyruvylated xanthan gum or reduced-pyruvylated xanthangum, carageenan, or a combination thereof. Preferably, it does notcontain a combination of starch and carrageenan or a combination ofcasein and waxy maize starch.

In the context of this disclosure, xanthan gum is food grade and can becommercially obtained from numerous suppliers. Xanthan gum is a highmolecular weight, long chain polysaccharide composed of the sugarsglucose, mannose, and glucuronic acid. The backbone is similar tocellulose, with added side chains of trisaccharides. Galactomannans arepolysaccharides made of a mannose backbone with (single) side chains ofgalactose units. The ratio of galactose to mannose differs in differentgalactomannans, with usually the majority being mannose. Glucomannansare polysaccharides mainly unbranched with a backbone comprised ofD-glucose and D-mannose residues. Usually approximately 60% of thepolysaccharide is made up of D-mannose and approximately 40% ofD-glucose. In the context of the present disclosure, galactomannans andglucomannans are food grade and can be commercially obtained fromnumerous suppliers.

High molecular weight proteins may include, for example,collagen-derived proteins such as gelatin, plant proteins such aspotato, pea, lupin, etc., or other proteins of sufficiently highmolecular weight (MW=100 kDa and above).

Synthetic polymers must be capable of use as food additives and mayinclude, for example, polyethyleneoxide (“PEO”) or polyvinylpyrrolidone(“PVP”). PEO is a particularly useful synthetic polymer in that it isacceptable as a food grade additive and only slightly increases theshear viscosity of a composition when present in low concentrations,while also strongly enhancing the extensional viscosity and cohesivenessof a material such as, for example, water. PEO also has a relativelyhigh Trouton ratio. PVP is also a synthetic polymer that can be used infood. There are known synergistic effects of an anionic surfactant withPVP, although the specific surfactant for which this has beendemonstrated, sodium lauryl sulfate (“SDS”), cannot be used with food.

Chemically modified polymers include chemically modified biopolymerssuch as, but not limited to, carboxymethylcellulose.

Compositions having a high Trouton ratio generally provide enhancedextensional viscosity and, thus, enhanced cohesiveness of the products.Generally speaking most simple liquids like oils and other Newtonianfluids have a Trouton ratio of about 3. For most non-Newtonian polymermelts, the Trouton ratio is greater than 3. In an embodiment, thenutritional products of the present disclosure have a Trouton ratio thatis at least about 6, preferably from about 6 to about 15. In anembodiment, the Trouton ratio is about 10. In an embodiment, theextensional viscosity of the nutritional product is greater than about100 mPa s.

In an embodiment, the inventive nutritional products comprise a sourceof protein. The protein source may be dietary protein including, but notlimited to animal protein (such as meat protein or egg protein), dairyprotein (such as casein, caseinates (e.g., all forms including sodium,calcium, potassium caseinates), casein hydrolysates, whey (e.g., allforms including concentrate, isolate, demineralized), whey hydrolysates,milk protein concentrate, and milk protein isolate)), vegetable protein(such as soy protein, wheat protein, rice protein, and pea protein), orcombinations thereof. In an embodiment, the protein source is selectedfrom the group consisting of whey, chicken, corn, caseinate, wheat,flax, soy, carob, pea, or combinations thereof.

In an embodiment, the inventive nutritional products comprise a sourceof carbohydrates. Any suitable carbohydrate may be used in the presentnutritional products including, but not limited to, sucrose, lactose,glucose, fructose, corn syrup solids, maltodextrin, modified starch,amylose starch, tapioca starch, corn starch or combinations thereof.

In an embodiment, the inventive nutritional products include a source offat. The source of fat may include any suitable fat or fat mixture. Forexample, the fat source may include, but is not limited to, vegetablefat (such as olive oil, corn oil, sunflower oil, rapeseed oil, hazelnutoil, soy oil, palm oil, coconut oil, canola oil, lecithins, and thelike), animal fats (such as milk fat) or combinations thereof.

In an embodiment, the inventive nutritional products further include oneor more prebiotics. Non-limiting examples of prebiotics include acaciagum, alpha glucan, arabinogalactans, beta glucan, dextrans,fructooligosaccharides, fucosyllactose, galactooligosaccharides,galactomannans, gentiooligosaccharides, glucooligosaccharides, guar gum,inulin, isomaltooligosaccharides, lactoneotetraose, lactosucrose,lactulose, levan, maltodextrins, milk oligosaccharides, partiallyhydrolyzed guar gum, pecticoligosaccharides, resistant starches,retrograded starch, sialooligosaccharides, sialyllactose,soyoligosaccharides, sugar alcohols, xylooligosaccharides, theirhydrolysates, or combinations thereof.

In an embodiment, the inventive nutritional products further include oneor more probiotics. Non-limiting examples of probiotics includeAerococcus, Aspergillus, Bacteroides, Bifidobacterium, Candida,Clostridium, Debaromyces, Enterococcus, Fusobacterium, Lactobacillus,Lactococcus, Leuconostoc, Melissococcus, Micrococcus, Mucor, Oenococcus,Pediococcus, Penicillium, Peptostrepococcus, Pichia, Propionibacterium,Pseudocatenulatum, Rhizopus, Saccharomyces, Staphylococcus,Streptococcus, Torulopsis, Weissella, or combinations thereof.

One or more amino acids may also be present in the inventive nutritionalproducts. Non-limiting examples of amino acids include alanine,arginine, asparagine, aspartate, citrulline, cysteine, glutamate,glutamine, glycine, histidine, hydroxyproline, hydroxyserine,hydroxytyrosine, hydroxylysine, isoleucine, leucine, lysine, methionine,phenylalanine, proline, serine, taurine, threonine, tryptophan,tyrosine, valine, or combinations thereof.

In an embodiment, the inventive nutritional products further include oneor more synbiotics, sources of ω-3 fatty acids, and/or phytonutrients.As used herein, a synbiotic is a supplement that contains both aprebiotic and a probiotic that work together to improve the microfloraof the intestine. Non-limiting examples of sources of ω-3 fatty acidssuch α-linolenic acid (“ALA”), docosahexaenoic acid (“DHA”) andeicosapentaenoic acid (“EPA”) include fish oil, krill, poultry, eggs, orother plant or nut sources such as flax seed, walnuts, almonds, algae,modified plants, etc. Non-limiting examples of phytonutrients includequercetin, curcumin and limonin.

One or more antioxidants may also be present in the inventivenutritional products. Non-limiting examples of antioxidants includecarotenoids, coenzyme Q10 (“CoQ10”), flavonoids, glutathione Goji(wolfberry), hesperidin, lactowolfberry, lignan, lutein, lycopene,polyphenols, selenium, vitamin A, vitamin B1, vitamin B6, vitamin B12,vitamin C, vitamin D, vitamin E, zeaxanthin, or combinations thereof.

The inventive nutritional products may also include fiber or a blend ofdifferent types of fiber. The fiber blend may contain a mixture ofsoluble and insoluble fibers. Soluble fibers may include, for example,fructooligosaccharides, acacia gum, inulin, etc. Insoluble fibers mayinclude, for example, pea outer fiber.

The inventive nutritional products may also include other functionalingredients including chitosans and protein aggregates. Chitosans arelinear polysaccharides composed of randomly distributed 13-(1-4)-linkedD-glucosamine (deacetylated unit) and N-acetyl-D-glucosame (acetylatedunit). Among other potential benefits, chitosans have naturalantibacterial properties, aid in drug delivery, and are known to rapidlyclot blood. Protein aggregates are coalescences of miss-folded proteinsdriven by interactions between solvent-exposed hydrophobic surfaces thatare normally buried within a protein's interior.

In still yet another embodiment, methods for making a nutritionalproduct are provided, wherein the nutritional product is preferably asdefined herein. The methods include providing a nutritional compositionand adding a food grade polymer to the nutritional composition to form anutritional product, preferably as defined herein, having a Troutonratio that is at least about 6, preferably from about 6 to about 15. Inan embodiment, an extensional viscosity of such product is greater than100 mPas. In yet another embodiment, methods for improving thecohesiveness of a nutritional product are provided. The methods includeadding to a nutritional composition a food grade polymer to form anutritional product, the food grade polymer being capable of improving acohesiveness of the nutritional composition such that the nutritionalproduct does not break-up during consumption of the nutritional product.In an embodiment, an extensional viscosity of the product is greaterthan 100 mPa s. In an embodiment, a Trouton ratio of the nutritionalproduct is at least 6, preferably from about 6 to about 15, and mostpreferably about 10.

In still yet another embodiment, methods for promoting safe swallowingof food boluses are provided. The methods include adding to anutritional composition a food grade polymer to form a nutritionalproduct, preferably as defined herein, the food grade polymer beingcapable of improving a cohesiveness of the nutritional composition suchthat the nutritional product does not break-up during consumption of thenutritional product, and administering the nutritional product to apatient in need of same. In an embodiment, an extensional viscosity ofthe product is greater than 100 mPas. In an embodiment, a Trouton ratioof the nutritional product is at least 6, preferably from about 6 toabout 15, and most preferably about 10.

In yet another embodiment, methods for preventing and/or treating apatient having a disease as defined herein, preferably a swallowingdisorder are provided. The methods include administering to a patient inneed of same a nutritional product, preferably as defined herein, morepreferably an effective amount of such a nutritional product, comprisinga nutritional composition and a food grade polymer, the nutritionalproduct having a Trouton ration that is at least 6, preferably fromabout 6 to about 15, and most preferably about 10. In an embodiment, anextensional viscosity of such product is greater than 100 mPa s. Hence,the inventive nutritional product may be used for preventing and/ortreating a patient having a swallowing disorder, preferably forprevention and/or treatment of dysphagia, but also for prevention and/ortreatment of malnourishment or undernourishment associated withdysphagia, preferably as mentioned above, such as e.g. silentaspiration, pneumonia, aspiration pneumonia, dehydration, pressureulcers, etc. Treatment also may be accomplished with regard to dysphagiapatients or patients highly susceptible of dysphagia or at risk ofdeveloping dysphagia, such as patients suffering from stroke,Parkinson's, Alzheimer's, Brain Damage and Multiple Sclerosis.

When treating a patient in need of such a treatment an effective amount,preferably one or more dosage units, of the inventive nutritionalproduct may be administered suitable for the patient to be treated anddepending on the specific requirements of such treatment. Such a dosageunit may have the form of a complete food, i.e. it may meet all (daily)nutritional needs of the patient, or may be a supplement or incompletefood. When provided as a supplement or incomplete food, several dosageunits preferably form a complete food, e.g. 2, 3, 4 or even 5 or more.The inventive nutritional product may thus be administered either insingle or in multiple dosage units per day. Multiple dosage units may beadministered either in separated meals during the same meal. As acomplete food, the inventive nutritional product preferably may containfrom about 200 to about 3000 kcal per daily dosage/dosage unit, morepreferably from about 250 to about 3000 kcal per daily dosage/dosageunit, even more preferably from about 500 to about 2500 or even fromabout 100 to about 2500 kcal per daily dosage/dosage unit. As anincomplete food, the inventive nutritional product preferably maycontain from about 200 to about 1500 kcal per dosage unit, morepreferably from about 200 to about 1000 kcal per dosage unit, even morepreferably from about 200 to about 500 kcal per dosage unit. The dosageunits are preferably calculated with respect to a mean daily energysupply of 2000 kcal to a healthy adult having a body weight of 70 kg.For persons of different condition and different body weight, the levelis preferably adapted accordingly. Such dosage units are preferablydefined as physically identifiable separate units, usually in packagedform.

In an embodiment, the food grade polymer is selected from the groupconsisting of plant-extracted gums, plant-derived mucilages andcombinations thereof, preferably as already defined above. Theplant-extracted gums are selected from the group consisting of okra gum,konjac mannan, tara gum, locust bean gum, guar gum, fenugreek gum,tamarind gum, cassia gum, acacia gum, gum ghatti, pectins, cellulosics,tragacanth gum, karaya gum, or any combinations thereof. In a preferredembodiment the plant-extracted gum is okra gum. The plant-derivedmucilages may be selected from the group consisting of cactus mucilage(Ficus indica), psyllium mucilage (Plantago ovata), mallow mucilage(Malva sylvestris), flax seed mucilage (Linum usitatissimum),marshmallow mucilage (Althaea officinalis), ribwort mucilage (Plantagolanceolata), mullein mucilage (Verbascum), cetraria mucilage (Lichenislandicus), or any combinations thereof. In a preferred embodiment, theplant-derived mucilage is cactus mucilage (Ficus indica). It isparticularly preferred that the food grade polymer is selected from okragum and/or cactus mucilage (Ficus indica), or a combination thereof. Ina further preferred embodiment, the plant-extracted gums and/or theinventive nutritional product do not contain starch, such as waxy maizestarch, xanthan gum, modified xanthan gum such as non-pyruvylatedxanthan gum or reduced-pyruvylated xanthan gum, carageenan, or acombination thereof. Preferably, it does not contain a combination ofstarch and carrageenan or a combination of casein and waxy maize starch.

By using the improved nutritional products as defined herein and methodsof making and administering same, the nutritional intake of dysphagicpatients may be improved by enabling them to swallow a wider variety offood and beverage products safely and comfortably. Such advantages maybe achieved by improving the cohesiveness of a food bolus, which lendsto the confidence of the patient in being able to consume a variety ofproducts without the food bolus breaking up and possibly being aspiratedby the patient. Such nutritional improvements may lead to an overallhealthier condition of the patient and prevent further health-relateddecline.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present subjectmatter and without diminishing its intended advantages. It is thereforeintended that such changes and modifications be covered by the appendedclaims.

The invention is claimed as follows: 1: A method of treating anindividual having a swallowing disorder, the method comprising:administering an effective amount of a liquid nutritional product to theindividual having the swallowing disorder, the liquid nutritionalproduct comprising a nutritional composition and a plant-derivedmucilage, the liquid nutritional product comprises an amount of theplant mucilage such that the liquid nutritional product has an increasedcohesiveness relative to the nutritional composition and has a Troutonratio of 6 to
 15. 2: The method of claim 1, wherein the liquidnutritional product has an extensional viscosity greater than 100 mPa s.3: The method of claim 1, wherein the plant-derived mucilage is selectedfrom the group consisting of cactus mucilage, psyllium mucilage, mallowmucilage, flax seed mucilage, marshmallow mucilage, ribwort mucilage,mullein mucilage, cetraria mucilage, and mixtures thereof. 4: The methodof claim 1, wherein the liquid nutritional product has a Trouton ratioof about
 10. 5: The method of claim 1, wherein the swallowing disorderis at least one of dysphagia or compromised saliva excretion. 6: Themethod of claim 1, wherein the liquid nutritional product has a formselected from the group consisting of pharmaceutical formulations,nutritional formulations, dietary supplements, functional food andbeverage products, and combinations thereof. 7: The method of claim 1,wherein the liquid nutritional product does not contain any starch, doesnot contain any xanthan gum, and does not contain any carrageenan. 8:The method of claim 1, wherein the liquid nutritional product furthercomprises an additional ingredient selected from the group consisting ofa probiotic, a prebiotic, an amino acid, a fatty acid, a phytonutrient,an antioxidant, and mixtures thereof. 9: A method of replacing saliva inan individual in need thereof, the method comprising: administering aneffective amount of a liquid nutritional product to the individual, theliquid nutritional product comprising a nutritional composition and afood-grade polymer, the liquid nutritional product comprises an amountof the food-grade polymer such that the liquid nutritional product hasan increased cohesiveness relative to the nutritional composition andhas a Trouton ratio of 6 to
 15. 10: The method of claim 9, wherein theliquid nutritional product has an extensional viscosity greater than 100mPa s. 11: The method of claim 9, wherein the food-grade polymer isselected from the group consisting of a plant-extracted gum, aplant-derived mucilage, and mixtures thereof. 12: The method of claim11, wherein the plant-extracted gum is selected from the groupconsisting of okra gum, konjac mannan, tara gum, locust bean gum, guargum, fenugreek gum, tamarind gum, cassia gum, acacia gum, gum ghatti,pectins, cellulosics, tragacanth gum, karaya gum, and mixtures thereof.13: The method of claim 11, wherein the plant-derived mucilage isselected from the group consisting of cactus mucilage, psylliummucilage, mallow mucilage, flax seed mucilage, marshmallow mucilage,ribwort mucilage, mullein mucilage, cetraria mucilage, and mixturesthereof. 14: The method of claim 1, wherein the liquid nutritionalproduct has a Trouton ratio of about
 10. 15: The method of claim 1,wherein the individual has at least one of dysphagia or compromisedsaliva excretion. 16: The method of claim 1, wherein the liquidnutritional product has a form selected from the group consisting ofpharmaceutical formulations, nutritional formulations, dietarysupplements, functional food and beverage products, and combinationsthereof. 17: The method of claim 1, wherein the liquid nutritionalproduct does not contain any starch, does not contain any xanthan gum,and does not contain any carrageenan. 18: The method of claim 1, whereinthe liquid nutritional product further comprises an additionalingredient selected from the group consisting of a probiotic, aprebiotic, an amino acid, a fatty acid, a phytonutrient, an antioxidant,and mixtures thereof.